Optimization and characterization of deoxypodophyllotoxin loaded mPEG-PDLLA micelles by central composite design with response surface methodology.
10.1016/S1875-5364(18)30081-5
- Author:
Ying-Lan YU
1
;
Ya-Nan LI
1
;
Yong ZHANG
2
;
Ru-Ning SUN
3
;
Jia-Sheng TU
1
;
Yan SHEN
4
Author Information
1. Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
2. Children's Hospital of Nanjing Medical University, Nanjing 210008, China.
3. Department of Professional Institute, China Pharmaceutical University, Nanjing 210009, China.
4. Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China. Electronic address: shenyan19820801@126.com.
- Publication Type:Journal Article
- Keywords:
Central composite design;
Cytotoxicity;
Deoxypodophyllotoxin;
Micelles
- MeSH:
Antineoplastic Agents;
chemistry;
toxicity;
Cell Survival;
drug effects;
Drug Carriers;
chemistry;
Drug Delivery Systems;
methods;
Drug Design;
HeLa Cells;
Humans;
Micelles;
Particle Size;
Podophyllotoxin;
analogs & derivatives;
chemistry;
toxicity;
Polyesters;
chemistry;
Polyethylene Glycols;
chemistry;
Solubility;
Surface Properties
- From:
Chinese Journal of Natural Medicines (English Ed.)
2018;16(6):471-480
- CountryChina
- Language:English
-
Abstract:
The therapeutic application of deoxypodophyllotoxin (DPT) is limited due to its poor water solubility and stability. In the present study, the micelles assembled by the amphiphilic block copolymers (mPEG-PDLLA) were constructed to improve the solubility and safety of DPT for their in vitro and in vivo application. The central composite design was utilized to develop the optimal formulation composed of 1221.41 mg mPEG-PDLLA, the weight ratio of 1 : 4 (mPEG-PDLLA : DPT), 30 mL hydration volume and the hydration temperature at 40 °C. The results showed that the micelles exhibited uniformly spherical shape with the diameter of 20 nm. The drug-loading and entrapment efficiency of deoxypodophyllotoxin-polymeric micelles (DPT-PM) were about (20 ± 2.84)% and (98 ± 0.79)%, respectively, indicating that the mathematical models predicted well for the results. Compared to the free DPT, the cytotoxicity showed that blank micelles possessed great safety for Hela cells. In addition, the DPT loaded micelle formulation achieved stronger cytotoxicity at the concentration of 1 × 10 mol·L, which showed significant difference from free DPT (P < 0.05). In conclusion, the micelles were highly promising nano-carriers for the anti-tumor therapy with DPT.
